{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:52:10Z","timestamp":1792446730777,"version":"4.5.0"},"reference-count":151,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["308844\/2025-4"],"award-info":[{"award-number":["308844\/2025-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the circulatory system and internal organs of the body are commonly observed in a number of cardiovascular diseases such as hypertension, diabetes, atherosclerosis, coronary artery disease, aortic aneurysm, atrial fibrillation, myocardial infarction, and heart failure, which are associated with the development of oxidative stress and myocardial inflammation. The adverse effects of AGEs on the cardiovascular system are elicited by both non-receptor mechanisms involving the cross-linking of extracellular and intracellular proteins, and by receptor-mediated mechanisms involving the binding of AGEs with advanced glycation end-product receptors (RAGEs) on the cell membrane. AGE\u2013RAGE interactions along with the cross-linking of proteins promote the generation of oxidative stress, the production of inflammation, the occurrence of intracellular Ca2+-overload, and alterations in the extracellular matrix leading to the development of cardiovascular dysfunction. AGEs also bind with two other protein receptors in the circulatory system: soluble RAGEs (sRAGEs) are released upon the proteolysis of RAGEs due to the activation of matrix metalloproteinase, and endogenous secretory RAGEs (esRAGEs) are secreted as a spliced variant of endogenous RAGEs. While the AGE\u2013RAGE signal transduction axis serves as a pathogenic mechanism, both sRAGEs and esRAGEs serve as cytoprotective interventions. The serum levels of sRAGEs are decreased in ischemic heart disease, vascular disease, and heart failure, as well as in other cardiovascular diseases, but are increased in chronic diabetes and renal disease. Several interventions which can reduce the formation of AGEs, block the AGE\u2013RAGE axis, or increase the levels of circulating sRAGEs have been shown to exert beneficial effects in diverse cardiovascular diseases. These observations support the view that the AGE\u2013RAGE axis not only plays a critical role in pathogenesis, but is also an excellent target for the treatment of cardiovascular disease.<\/jats:p>","DOI":"10.3390\/ijms26157311","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T09:31:45Z","timestamp":1753781505000},"page":"7311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Role of Advanced Glycation End-Products in the Pathophysiology and Pharmacotherapy of Cardiovascular Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Karina O.","family":"Mota","sequence":"first","affiliation":[{"name":"Department of Physiology, Center of Biological and Health Sciences, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M. L.","family":"de Vasconcelos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Center of Biological and Health Sciences, Federal University of Sergipe, S\u00e3o Crist\u00f3v\u00e3o 49100-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorrie A.","family":"Kirshenbaum","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naranjan S.","family":"Dhalla","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jacc.2014.10.024","article-title":"Healthy lifestyle in the primordial prevention of cardiovascular disease among young women","volume":"65","author":"Chomistek","year":"2015","journal-title":"J. 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